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  • 1
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    Gene of the month: Axl (2016)
    BMJ Publishing Group
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    Publication Date: 2016-04-21
    Description: The interaction between Axl receptor tyrosine kinase and its main ligand Gas6 has been implicated in the progression of a wide number of malignancies. More recently, overexpression of Axl has emerged as a key molecular determinant underlying the development of acquired resistance to targeted anticancer agents. The activation of Axl is overexpression-dependent and controls a number of hallmarks of cancer progression including proliferation, migration, resistance to apoptosis and survival through a complex network of intracellular second messengers. Axl has been noted to influence clinically meaningful end points including metastatic recurrence and survival in the vast majority of tumour types. With Axl inhibitors having gained momentum as novel anticancer therapies, we provide an overview of the biological and clinical relevance of this molecular pathway, outlining the main directions of research.
    Print ISSN: 0021-9746
    Electronic ISSN: 1472-4146
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 2
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    Anatomical basis and histopathological changes resulting from selective internal radiotherapy for liver metastases (2013)
    BMJ Publishing Group
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    Publication Date: 2013-02-23
    Description: Background Knowledge that liver tumours preferentially take their blood supply from the arterial blood supply rather than the portal venous system can be used for local delivery of treatment or for embolisation to cut off the blood supply to tumours. Aims To present histological evaluation of malignant and non-malignant hepatic tissue of one such therapy, selective internal radiation therapy (SIRT) with yttrium-90 microspheres, to decipher its principal mechanism of action. Methods The H&E stained sections of hepatic resection specimens from three patients with liver metastases from colorectal (CRC) cancer, who underwent hepatic surgery 4–9 months following SIRT, were examined and the pathological changes documented. Results Resin microspheres were identified in the vascular tumour bed and vessels within the portal tracts of the background liver parenchyma. Microspheres were usually associated with giant cell reaction or histiocytes. In the tumour bed, tumour necrosis, mucinous alteration, collections of foamy histiocytes, ectatic vessels, calcification and fibrosis were observed. There was minimal cellular inflammatory response observed, suggestive of direct radiation injury as a non-immune mediated process. Conclusions We describe in detail the spectrum of histopathological changes in malignant tissue and liver parenchyma in patients with metastatic CRC treated with SIRT. Our findings are consistent with the hypothesis that the principal mechanism of action of SIRT appears to be via arterially directed delivery of highly radioactive microspheres in and around the vascular tumour bed rather than by micro-arterial embolisation.
    Keywords: Open access, Immunology (including allergy), Hepatic cancer, Inflammation, Clinical diagnostic tests
    Print ISSN: 0021-9746
    Electronic ISSN: 1472-4146
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 3
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    Pathological grading of regression following neoadjuvant chemoradiation therapy: the clinical need is now (2012)
    BMJ Publishing Group
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    Publication Date: 2012-09-23
    Description: Neoadjuvant chemoradiotherapy for locally advanced rectal cancer has been shown to decrease rates of local recurrence and more than double the rate of sphincter-preserving surgery. There is now compelling evidence that pathological complete response is an independent predictor of likelihood of local recurrence, distal metastases, disease-free and overall survival in locally advanced rectal cancer following neoadjuvant chemoradiotherapy. Pathological regression grading can therefore guide clinical decisions about salvage surgical strategies, adjuvant therapy and long-term surveillance. No universally recognised regression grading system currently exists for pathologists presented with resected tumour specimens following neoadjuvant chemoradiotherapy. The purpose of this review is to highlight the relevance of accurate tumour regression grading in achieving optimal clinical care for patients with rectal cancer.
    Keywords: Editor's choice, Immunology (including allergy), Colon cancer
    Print ISSN: 0021-9746
    Electronic ISSN: 1472-4146
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 4
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    NKX3.1 is expressed in ER-positive and AR-positive primary breast carcinomas (2014)
    BMJ Publishing Group
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    Publication Date: 2014-08-20
    Description: Aims NKX3.1 is an androgen-regulated tumour suppressor gene that is downregulated in prostate carcinoma. Immunohistochemistry for NKX3.1 is primarily specific for prostatic-derived tumours and tissue but is reported in a small number of breast carcinomas. NKX3.1 is also shown to inhibit estrogen receptor (ER) signalling in breast carcinoma models. Here, we investigate labelling of NKX3.1 in invasive ductal (IDC) and lobular (ILC) carcinomas of the breast with full characterisation of ER, progesterone receptor (PR), androgen receptor (AR) and Her2 status. Methods Tissue microarrays of 86 primary IDC and 37 ILC were labelled for NKX3.1. The IDC consisted of 20 luminal A, 7 luminal B, 14 Her2, and 45 triple negative carcinomas. The ILC consisted of 34 luminal A and 3 luminal B cases. NKX3.1 expression was scored as percentage nuclear labelling and labelling intensity. Results Nuclear NKX3.1 labelling was seen in 2 IDC (2%) and 10 ILCs (27%). labelling intensity was weak in all cases (1–100% nuclear positivity). Positive NKX3.1 labelling was significantly associated with ILC (p〈0.0001). NKX3.1 labelling was seen only in ER and AR-positive carcinomas, which showed a significant correlation (p=0.0003 and p=0.0079, respectively). Expression was not correlated with tumour stage, size, Her2 expression, presence of lymph node metastases or age. Conclusions This is the first study to evaluate NKX3.1 expression in breast carcinomas with known ER, PR, AR and Her2 status. Further studies are needed to evaluate what potential role NKX3.1 plays in ER and AR signalling and hormonal treatment response in breast carcinomas.
    Keywords: Immunology (including allergy), Breast cancer, Prostate cancer, Urological cancer
    Print ISSN: 0021-9746
    Electronic ISSN: 1472-4146
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 5
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    CD24: a potential new marker in differentiating malignant mesothelioma from pulmonary adenocarcinoma (2013)
    BMJ Publishing Group
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    Publication Date: 2013-02-23
    Description: Background The differential diagnosis between malignant mesothelioma (MM) and metastatic lung adenocarcinoma (MLA) often relies on immunohistochemical studies, with no individual immunomarker holding satisfactory discrimination ability. Methods We investigated the diagnostic accuracy of CD24 immunoreactivity on 134 patients including 69 cases of MM and 65 MLA. Results The expression of CD24 favoured MLA, with 57/65 cases showing positive cytoplasmic staining compared with 9/69 MM (p〈0.001), whose immunopositivity pattern was prevalently membranous (7/9 cases). Conclusions CD24 positivity can accurately discriminate MM from MLA. Prospective studies are warranted to clarify whether CD24 could integrate with other immunomarkers to facilitate the diagnosis of mesothelial malignancies.
    Keywords: Immunology (including allergy), Lung cancer (oncology), Respiratory cancer, Lung cancer (respiratory medicine)
    Print ISSN: 0021-9746
    Electronic ISSN: 1472-4146
    Topics: Medicine
    Published by BMJ Publishing Group
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  • 6
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    Not useful in modern healthcare (2012)
    BMJ Publishing Group
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    Publication Date: 2012-07-24
    Description: I completely agree with Spence.1 He raised an issue that many find controversial although it is as clear as water.Physical signs are unreliable and usually have very high interobserver variability,...
    Topics: Medicine
    Published by BMJ Publishing Group
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